Safety of Tdap Vaccine During Pregnancy Backed by New Review

By Reuters Staff

February 10, 2017

NEW YORK (Reuters Health) - A literature review offers reassuring data on the safety of tetanus, diphtheria and acellular pertussis (Tdap) vaccination in pregnant women, industry-funded researchers say.

"Evidence suggests that antenatal combined Tdap administered during the second or third trimester of pregnancy is not associated with clinically significant harms for the fetus or neonate," report Mark McMillan from the University of Adelaide, Australia, and colleagues in Obstetrics and Gynecology, online February 6.

They note that many countries are experiencing a "resurgence" of pertussis, despite high rates of childhood vaccination coverage. Infants younger than two months of age, who are too young to be fully protected from active immunization, are most vulnerable.

Therefore, many countries including the U.S., U.K. and Australia now advise pertussis-containing vaccines for pregnant women in the third trimester or earlier to protect babies younger than two months of age. Yet, there is limited information about the safety of antenatal vaccination for the mother, fetus and newborn.

To investigate, McMillan and colleagues did a systematic review of 21 studies reporting adverse effects in pregnant women, fetuses, and infants after antenatal immunization with vaccines containing pertussis antigens, diphtheria toxoid, tetanus toxoid, or inactivated polio antigens.

Studies assessing adverse birth outcomes such as preterm birth, small-for-gestational-age (SGA), stillbirth, low birthweight, and congenital anomalies "do not suggest an increased risk after antenatal Tdap or Tdap-IPV exposure in late second or third trimester of pregnancy," they report. All 95% confidence intervals for outcomes estimates spanned 1.0. However, these observations are based largely on low-level retrospective data, they note.

There was no statistically or clinically significant risk for hypertensive disorders or preterm labor. There was a small but statistically significant increased risk of chorioamnionitis in one large retrospective study, they say, but no increased risk of preterm birth, a major sequela of chorioamnionitis. The researchers say adequately powered studies looking at associations between antenatal Tdap vaccination and chorioamionitis are needed.

"Point estimates for all anomalies after antenatal tetanus toxoid vaccination ranged from 1.20 to 1.60 and had 95% CIs that crossed 1.0," the researchers report. "Further homogenous studies that report individual congenital anomaly outcomes after first-trimester antenatal vaccination would also be beneficial."

In addition, the studies they reviewed contained "few" reports of severe reactions after vaccination. The most common adverse events were local reactions. "Objective rates of fever were low, 3% or below, and more common systemic events observed included headache, malaise, and myalgia," they write.

The researchers note that due to the change in recommendations in many countries to give the Tdap vaccine in pregnancy, it's likely the number of studies looking at the safety of antenatal Tdap vaccination will increase in the near future.

"Studies are currently underway that will add rapidly to this body of evidence. Postmarketing surveillance data from countries that have antenatal Tdap programs will also provide valuable evidence," they say.

GlaxoSmithKline and Sanofi Pasteur provided research grants for this investigator-led study.


Obstet Gynecol 2017.